The career development and research program described in this proposal support the application for an ADAMHA Scientist Development Award (SDA, K21) for Dr. Athina Markou, and is intended to provide the candidate with the background knowledge, research experience, and research management skills that will take place in the Department of Neuropharmacology (Dr. Floyd E. Bloom, Chair) of The Scripps Research Institute, under the direct supervision of Dr. George F. Koob and Dr. Friedbert Weiss. Dr Koob is highly qualified to serve as Preceptor for the Candidate, because of his experience with the research methodologies to be used, his active research program in drug abuse, and his commitment to the development of junior research scientists. The Department of Neuropharmacology emphasizes a multi-disciplinary approach to problems of drug addiction and mental disorders. Thus, this is an ideal environment for the Candidate to materialize her goal of a multidisciplinary research approach to the neurobiology of drug abuse. The overall objective of the research plan is to explore the role of the amygdala, and amygdala- accumbens and amygdala-hypothalamus interactions in incentive- motivational paradigms that assess the incentive-motivational and reward values of reinforcers (e.g., cocaine and intracranial self-stimulation) with state-of-the-art neurochemical and neuroanatomical techniques. The proposed studies will explore the potential role(s) of dopamine and serotonin release in the amygdala in cocaine self-administration behavior, using the in vivo microdialysis technique. Further, through the use of selective neurotoxic and excitotoxic lesions, the role of the amygdala connection to the accumbens in cocaine self-administration behavior will be investigated. Moreover, the role(s) of the amygdala, the nucleus accumbens, and the amygdala-accumbens interaction in the control exerted over behavior by conditioned stimuli associated with cocaine infusions will be explored. The study of the neurobiological substrates of conditioned reinforcers may provide valuable insights about the neurobiological processes mediating drug-seeking behavior (i.e., drug craving). Similar microdialysis and lesion studies will be conducted with intracranial self-stimulation as the reinforcer to further explore the role of the amygdala accumbens and amygdala-hypothalamus interactions in incentive-motivational and reward processes. These studies promise to yield new insights regarding the role of the amygdala and its efferent in reward processes and drug abuse and have implications for the etiology, prevention, and treatment of drug dependence.